Design and implementation of large-scale genetic association studies of common diseases. (360G-Wellcome-076113_G_04_Z)

We propose a pilot study to test the association of 100,000 specific polymorphisms with a range of common diseases using a two stage case-control study design. The study will include diabetes, breast cancer, cardiovascular disease, bipolar disorder, and other diseases (2,000 samples each), as well as two common control groups (up to 3,000 samples total) for further evaluation. Positive associations will form the basis for future biological studies. The results will be used to evaluate how best to optimise the design, implementation, analysis and cost efficiency of large-scale and genome-wide association studies in the future. We will examine features such as SNP selection, analysis methods, population structure, study size, the use of common controls, heterogeneity in sample collections, linkage disequilibrium and SNP tagging. The results will provide independent assessment of the coverage of SNP panels that are available to the community for genetic studies, including the output of the International HapMap Project. The project will help to establish a separate training programme in statistical genetics, and will lay the foundations for the development of an infrastructure for UK research in this area in future years.